Stiripentol

All FDA rules and regulations must be followed to import any medication used for personal use in the treatment of Rare and Genetic Diseases with the Orphan Drug Indication. The following links might provide helpful in understanding the rules and regulations.

Insurance Coverage, Research Papers, and Evidence Based Studies

Many insurance companies need proof that the medication has proven to be effective in treating the underlying disease or condition. The use of scientific studies, research papers or evidence based studies is a way to document and support your request for coverage of the Orphan Drug Stiripentol to treat Dravet Syndrome. Following a some research papers which do support the use of Stiripentol and its efficacy in treating Dravet Syndrome which might prove helpful in obtaining prior authorization through your insurance company.

Research Articles at Dravet.org has an update resource for Research Articles of interest and should be visited to keep abreast of new developments and ongoing research.

Private Insurance Coverage:

Each insurance company is different in the coverage of medications according to the policy issued to the employer and members. You may have to read their policies and procedures in addition to the appeal process to request the coverage. Keep in mind you will be denied based solely on the Non-FDA Approved status, even with the Orphan Drug Status indication.

Make the request for the stiripentol medication through the proper channels within the insurance company. You will be denied the medication because it is not FDA approved at this point in time. Once the denial has been received, this is where the important steps occur. Appeal the denial and site reasons for the administration of the medication, the cost benefits to the insurance company with reduced ER trips, ambulances and associated costs; fewer medications and less side effects; and fewer hospitalizations or shorter length of stay with each hospitalizations. Site the research supporting your request, but do not overload the request with too much information. Most importantly, wait for an answer to the appeal. Ask what the time frame for the appeal process (5 business days) and know your rights.

If the private insurance will not cover the stiripentol, then move to the state through Medicaid to get coverage. Each state has their own medicaid coverage of children with additional coverage for special needs children up to the age of 21 by EPSDT (Early Periodic Screening, Diagnosis and Treatment) which is not generally covered under private pay insurance or the regular medicaid insurance coverage.

Medicaid/Waiver/EPSDT Coverage:

Each state has a method to deliver medical care to children and the disabled. Medicaid is a federally funded program which is appropriated as deemed appropriate in each state. Every state has to comply with certain rules and regulations. One important rule is that disabled children have the right to treatment not otherwise covered with their insurance company. This includes the "compassionate use" of Orphan Drug medications and nursing services in addition to many other resources or services. Please check with your state to apply for Medicaid.

Once approved for Medicaid, the medically-fragile child needs to request a special-needs case manager. This level of case manager comes with a lighter case-load to handle the oversight of the higher level of needs and is a step to ensure that the child with increased needs does not get ignored.

Once Medicaid approved, request for the application for the EPSDT services. This expands the services available under Medicaid to include other services not otherwise covered.

Regardless of the delivery of medicaid insurance (straight medicaid, waiver or HMO) the use of stiripentol should be covered by the EPSDT if deemed medically necessary, other conventional anti-epileptic medications have failed (usually no more than 5 mono or poly-pharmacologic combinations) & the seizures are not responding to treatments, and there is a documented genetic mutation falling within the Dravet spectrum -or- there is a clinical presentation of SMEI/Dravet Syndrome diagnosis for the child.

Make the request for the stiripentol medication through the proper channels within the insurance company. You will be denied the medication because it is not FDA approved at this point in time. Once the denial has been received, this is where the important steps occur. Appeal the denial and site reasons for the administration of the medication, the cost benefits to the insurance company with reduced ER trips, ambulances and associated costs; fewer medications and less side effects; and fewer hospitalizations or shorter length of stay with each hospitalizations. Site the research supporting your request, but do not overload the request with too much information. Most importantly, wait for an answer to the appeal. Ask what the time frame for the appeal process (5 business days) and know your rights.

There are other states which currently are covering the stiripentol via Medicaid/EPSDT with the application of "Compassionate Use". The coverage in other states is precedence in the application of the use of the program which applies to prescribing the stiripentol. California has an example of how to approve the stiripentol and to avoid issues with coverage. Other states who currently cover the stiripentol are (in no particular order):

Biocodex

Biocodex is the manufacturer in France and the only authorized vendor for US insurance companies when importing the medication into the US for personal use. The reason for this limitation is that the Orphan Drug Status was provided to the manufacturer, not to resellers. The time for the first order is longer (approximately 2-3 weeks) but the cost is less when ordering from Biocodex. The subsequent orders are processed quickly and efficiently and arrive in about 1 weeks time. The invoice will be emailed and sent with the medication shipment. Terms on the invoice are due and payable within 60 days of the invoice and payable in Euros.

To order the medication you will need:

Prescription with the Stiripentol medication, dose, timing, frequency, route and number of month supply. PLEASE NOTE: The personal importation rules of the FDA do not allow more than a 3 months supply at any one time.

Letter of Medical Necessity for the STP, Confirmation of the Dravet Diagnosis, and the Plan of Treatment with a list of other medications at use for the time of administration. Include plans to decrease other medications appropriately to account for the slower liver metabolism which allows for increased serum levels of other AED medications being used concurrently.

Consent letter from the parent or guardian stating that the medication is for personal use only, is intended only for the person in which it is prescribed, that there is no intent to resell the medication or to distribute within the USA, and the parents acknowledge the Orphan Drug Status as not FDA approved.

INFORMATION FROM BIOCODEX TO ORDER DIRECTLY FROM THE PARENT COMPANY IN FRANCE:

Thank you for contacting Biocodex. Biocodex USA are a subsidiary of Biocodex, Inc. in France. Biocodex USA does not have this product and it is not yet approved in the United States. I can only give you the instructions to place an order with our parent company. I have been advised by Biocodex, Inc. of the following information to order Stiripentol - DIACOMIT. See below.

If you have any other questions or concerns, feel free to contact me; otherwise, this is as far as I can take you through the process for this product. From here, I suggest you inquire via email due to the time difference.

Source: Biocodex in Franace

The order can be submitted to [email protected] or by fax to +33 (0)1 41 24 30 04 or by courier to BIOCODEX ? Pharmaceutical Affairs ? 7 avenue Gallieni ? 94250 GENTILLY ? France.

You can redirect the request to the above mentioned address(es) so that our parent company may proceed with administrative work and papers to comply with US FDA regulation for non-approved drugs. They will manage things with parents/doctors/pharmacist in directly.

As you certainly know DIACOMIT® (stiripentol) has received a positive opinion for Marketing Authorisation from European health Authorities but is not yet approved in the US.

Indeed the drug has been recognized as effective in treating patients with Severe Myoclonic Epilepsy in Infancy (SMEI) / Dravet's syndrom, when associated to appropriate dosage of valproate and clobazam. (It is not planned to use it out of this indication because we have no information on its efficacy in other conditions).

The drug has to be sent directly to patient's parents according "FDA's personal importation rule". That means that the shipment must be accompanied by a statement that parents will have to sign and send us (see highlighted statement).

STATEMENT

To whom it may concern :

We, the undersigned parents of xxxxxxxxxxxxxxxxxxx [name of patient], certify that the present drug DIACOMIT (stiripentol) BIOCODEX is intended to be used only by our xxxxxxxx [daughter / son] for treating a serious condition for which no effective treatment is available. The drug is used under an Extended Access Program named Cohort Temporary Use Authorisation, in France , and in patient named procedure, in the UK. It is considered not to represent an unreasonable risk. The Dr [name, address], Medical Doctor, will be responsible for [her/his] treatment with the product.

[Name of parents + Signature]

So to provide patient with DIACOMIT, we will require following information:

an original consent from parents (duly signed) stating that they agree to administer this drug that is not approved in the USA,

an original prescription of the neurologist who treat the child (his name and address must be mentioned on the above statement),

the list of associated drugs

the exact address and phone number of parents to allow the express mail to deliver the drug,

first name, age, date of birth and weight of the child,

order information (quantity of product needed).

In a first step you (or parents) can send these documents to me by fax or e-mail, but I need original ones.

The FDA's personal importation rule doesn't allow us to supply the drug directly to doctors.

We can send a 3 months treatment (that is maximum authorized per shipment in the FDA's personal importation policy). You will also find attached our current price list. (Highlighted Area)

As of January 2013

STP 250 mg capsules (box of 60) 285 EURO

STP 500 mg capsules (box of 60) 570 EURO

STP 250 mg sachets (box of 60) 285 EURO

STP 500 mg sachets (box of 60) 570 EURO

Unfortunately, we don't have any patient assistance program which provides free or lower cost medication to families having difficulty paying for the drug.

The delivery time for USA is about 2 or 3 weeks (it depends on customs).

Concerning payment, the drug is invoiced after the shipment. This invoice can be paid either by credit card, by check or by bank transfer.

Caligor

Caligor Pharmacy is an import/export pharmacy which has the ability to obtain medications for use in clinical trails or for expanded access and unlicensed use. The pharmacy will dispense the medication through the New York store site or can make arrangements for shipment to a local neurologist or pharmacy. The order cannot be more than a three-month supply. Payment is due at the time the order is placed.

Follow up question in regards to the administration of the STP and Dairy Products related to the ketogenic diet dairy based meals...

Source: Biocodex - Carine Brodard, Pharmacist (via email 11/14/2011)

As we did not study potential interactions between milk and dairy product, we can not recommend to take stiripentol with these products. Moreover preliminary data indicated that the product could not be taken in empty stomach and therefore many patients were concerned by this recommendation as milk or dairy products were often used during meals. New data indicate that the product could be taken on empty stomach, therefore we propose that you give the stiripentol to your son away from meals (approx. 2 hours). This way, the risk (if it exists) of interaction with the dairy product would be reduced.

NJ Board of Nursing and the NJ Association of Nurses Response to NJ nurses administering the Orphan Drug when deemed medically necessary for a child. Nothing in nursing law would prevent a nurse from being able to administer an orphan drug ordered by licensed NJ physician if the nurse is educated about the medication and has the skills necessary to administer it. However, agencies do have the right to establish policies which may be more restrictive for their employees than existing law. I have been in contact with a community health nurse who provides specialty care for the Visiting Nurse Association of Central NJ. She relates that if she had all the information she needed on an orphan drug so that she could be aware of any special precautions regarding administration, all effects, side effects and drug interactions and the child's response to the first dose (which she would ask that the physician administer) and she had an order from a physician and the skills necessary to administer it, she would be willing to do so.

FDA and EMA Agreement July 2009 FDA announcement that the FDA and the EMEA will utilize similar practices and agree to share information for the development of medication to treat rare diseases and children.

Import Policy of the FDA Policy on importation of drugs by the FDA (1998). "...guidance does not specify that a U.S. citizen may import an unapproved drug only with a prescription from a U.S. licensed physician, or that a foreign citizen may import an unapproved new drug only with a foreign prescription. Rather, to ensure that the importation is for personal use only (and not for resale), and to ensure that the use of the unapproved new drug sought to be imported into the U.S. is supervised and does not represent an unreasonable risk, the guidance provides that the individual affirm in writing that the drug is for his or her personal use, and provide either the name and address of the U.S. licensed physician who will supervise its use or some evidence that the treatment was begun in a foreign country/area and that the drugs are being imported to continue/conclude the already begun treatment. Thus, while not the only documentation, either a U.S. or foreign prescription, along with an affirmation of personal use, could be supplied as evidence that this factor exists..."